@article{VellmerHartlebFraderaSolaetal.2022, author = {Vellmer, Tim and Hartleb, Laura and Fradera Sola, Albert and Kramer, Susanne and Meyer-Natus, Elisabeth and Butter, Falk and Janzen, Christian J.}, title = {A novel SNF2 ATPase complex in Trypanosoma brucei with a role in H2A.Z-mediated chromatin remodelling}, series = {PLoS Pathogens}, volume = {18}, journal = {PLoS Pathogens}, number = {6}, doi = {10.1371/journal.ppat.1010514}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301372}, year = {2022}, abstract = {A cascade of histone acetylation events with subsequent incorporation of a histone H2A variant plays an essential part in transcription regulation in various model organisms. A key player in this cascade is the chromatin remodelling complex SWR1, which replaces the canonical histone H2A with its variant H2A.Z. Transcriptional regulation of polycistronic transcription units in the unicellular parasite Trypanosoma brucei has been shown to be highly dependent on acetylation of H2A.Z, which is mediated by the histone-acetyltransferase HAT2. The chromatin remodelling complex which mediates H2A.Z incorporation is not known and an SWR1 orthologue in trypanosomes has not yet been reported. In this study, we identified and characterised an SWR1-like remodeller complex in T. brucei that is responsible for Pol II-dependent transcriptional regulation. Bioinformatic analysis of potential SNF2 DEAD/Box helicases, the key component of SWR1 complexes, identified a 1211 amino acids-long protein that exhibits key structural characteristics of the SWR1 subfamily. Systematic protein-protein interaction analysis revealed the existence of a novel complex exhibiting key features of an SWR1-like chromatin remodeller. RNAi-mediated depletion of the ATPase subunit of this complex resulted in a significant reduction of H2A.Z incorporation at transcription start sites and a subsequent decrease of steady-state mRNA levels. Furthermore, depletion of SWR1 and RNA-polymerase II (Pol II) caused massive chromatin condensation. The potential function of several proteins associated with the SWR1-like complex and with HAT2, the key factor of H2A.Z incorporation, is discussed.}, language = {en} } @article{SathyanarayanaLeeWrightetal.2018, author = {Sathyanarayana, Vijaya and Lee, Beth and Wright, Neville B. and Santos, Rui and Bonney, Denise and Wynn, Robert and Patel, Leena and Chandler, Kate and Cheesman, Ed and Schindler, Detlev and Webb, Nicholas J. A. and Meyer, Stefan}, title = {Patterns and frequency of renal abnormalities in Fanconi anaemia: implications for long-term management}, series = {Pediatric Nephrology}, volume = {33}, journal = {Pediatric Nephrology}, number = {9}, doi = {10.1007/s00467-018-3952-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227400}, pages = {1547-1551}, year = {2018}, abstract = {Fanconi anaemia (FA) is an inherited disease with bone marrow failure, variable congenital and developmental abnormalities, and cancer predisposition. With improved survival, non-haematological manifestations of FA become increasingly important for long-term management. While renal abnormalities are recognized, detailed data on patterns and frequency and implications for long-term management are sparse. We reviewed clinical course and imaging findings of FA patients with respect to renal complications in our centre over a 25-year period to formulate some practical suggestions for guidelines for management of renal problems associated with FA. Thirty patients including four sibling sets were reviewed. On imaging, 14 had evidence of anatomical abnormalities of the kidneys. Two cases with severe phenotype, including renal abnormalities, had chronic kidney disease (CKD) at diagnosis. Haematopoietic stem cell transplantation was complicated by significant acute kidney injury (AKI) in three cases. In three patients, there was CKD at long-term follow-up. All patients had normal blood pressure. Evaluation of renal anatomy with ultrasound imaging is important at diagnostic workup of FA. While CKD is uncommon at diagnosis, our data suggests that the incidence of CKD increases with age, in particular after haematopoietic stem cell transplantation. Monitoring of renal function is essential for management of FA. Based on these long-term clinical observations, we formulate some practical guidelines for assessment and management of renal abnormalities in FA.}, language = {en} } @article{DindasScherzerRoelfsemaetal.2018, author = {Dindas, Julian and Scherzer, S{\"o}nke and Roelfsema, M. Rob G. and Meyer, Katharina von and M{\"u}ller, Heike M. and Al-Rasheid, K. A. S. and Palme, Klaus and Dietrich, Petra and Becker, Dirk and Bennett, Malcolm J. and Hedrich, Rainer}, title = {AUX1-mediated root hair auxin influx governs SCFTIR1/AFB-type Ca2+ signaling}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-03582-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225368}, year = {2018}, abstract = {Auxin is a key regulator of plant growth and development, but the causal relationship between hormone transport and root responses remains unresolved. Here we describe auxin uptake, together with early steps in signaling, in Arabidopsis root hairs. Using intracellular microelectrodes we show membrane depolarization, in response to IAA in a concentration- and pH-dependent manner. This depolarization is strongly impaired in aux1 mutants, indicating that AUX1 is the major transporter for auxin uptake in root hairs. Local intracellular auxin application triggers Ca2+ signals that propagate as long-distance waves between root cells and modulate their auxin responses. AUX1-mediated IAA transport, as well as IAA- triggered calcium signals, are blocked by treatment with the SCFTIR1/AFB - inhibitor auxinole. Further, they are strongly reduced in the tir1afb2afb3 and the cngc14 mutant. Our study reveals that the AUX1 transporter, the SCFTIR1/AFB receptor and the CNGC14 Ca2+ channel, mediate fast auxin signaling in roots.}, language = {en} } @article{LeopoldBauerBechdolfetal.2020, author = {Leopold, Karolina and Bauer, Michael and Bechdolf, Andreas and Correll, Christoph U. and Holtmann, Martin and Juckel, Georg and Lambert, Martin and Meyer, Thomas D. and Pfeiffer, Steffi and Kittel-Schneider, Sarah and Reif, Andreas and Stamm, Thomas J. and Rottmann-Wolf, Maren and Mathiebe, Josephine and Kellmann, Eva L. and Ritter, Philipp and Kr{\"u}ger-{\"O}zg{\"u}rdal, Seza and Karow, Anne and Sondergeld, Lene-Marie and Roessner, Veit and Sauer, Cathrin and Pfennig, Andrea}, title = {Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study}, series = {Bipolar Disorders}, volume = {22}, journal = {Bipolar Disorders}, number = {5}, doi = {10.1111/bdi.12894}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215469}, pages = {517 -- 529}, year = {2020}, abstract = {Objective Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. Method In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30 years were randomized to 14 weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75\% of the targeted sample. Results Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8\%) vs unstructured group meetings (n = 37, completers = 78.4\%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs. Conclusions Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.}, language = {en} } @article{DopplerMeyerDovernetal.2019, author = {Doppler, Christopher E. J. and Meyer, Linda and Dovern, Anna and St{\"u}hmer-Beckh, Jaro and Weiss, Peter H. and Fink, Gereon R.}, title = {Differential impact of social and monetary reward on procedural learning and consolidation in aging and its structural correlates}, series = {Frontiers in Aging Neuroscience}, volume = {11}, journal = {Frontiers in Aging Neuroscience}, doi = {10.3389/fnagi.2019.00188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222394}, year = {2019}, abstract = {In young (n = 36, mean +/- SD: 24.8 +/- 4.5 years) and older (n = 34, mean +/- SD: 65.1 +/- 6.5 years) healthy participants, we employed a modified version of the Serial Reaction Time task to measure procedural learning (PL) and consolidation while providing monetary and social reward. Using voxel-based morphometry (VBM), we additionally determined the structural correlates of reward-related motor performance (RMP) and PL. Monetary reward had a beneficial effect on PL in the older subjects only. In contrast, social reward significantly enhanced PL in the older and consolidation in the young participants. VBM analyses revealed that motor performance related to monetary reward was associated with larger grey matter volume (GMV) of the left striatum in the young, and motor performance related to social reward with larger GMV of the medial orbitofrontal cortex in the older group. The differential effects of social reward in young (improved consolidation) and both social and monetary rewards in older (enhanced PL) healthy subjects point to the potential of rewards for interventions targeting aging-associated motor decline or stroke-induced motor deficits.}, language = {en} }